Gastroparesis (GP) is a disorder of gastric motilityfunction characterized by a delay in gastric emptying, frequently associated with chronic nausea and vomiting, early satiety, postprandial fullness, abdominal pain, and malnutrition that may require nutritional support. GP has a devastating impact on quality of life and predominantly affects younger women. In the past 5 years, the Gastroparesis Clinical Research Consortium (GpCRC) has made a series of important contributions to improve our understanding of this disorder and these observations have advenced the goals of helping our patients and their physicians as well as meeting the goals to improve the management of gastroparesis. We therefore propose the following specific aims for this application: # 1: To complete the ongoing and approved studies initiated by the GpCRC;# 2: To maintain, expand, and refine the GP Registry, and to address important questions related to the pathogenesis, complications and clinical outcome in GP patients by further in-depth analysis of GpR clinical data and biosamples;# 3: To conduct new multicenter studies of gastroparesis investigating the etiology, pathogenesis, diagnosis, and treatment options. TTUHSC is proposing a double-blind, "time- to- failure" placebo controlled trial (phase 1) of 4 months duration with "a best clinical care" follow up (phase 2) of 8 months duration study to evaluate the efficacy and safety of domperidone in gastroparesis. The principal objectives of this multicenter, randomized trial are to:1) Document the efficacy of domperidone in GP patients;2) Compare domperidone's efficacy in diabetics vs. idiopathic etiologies;3) Investigate the optimal dose or doses;4) Explore the demographic and clinical factors which predict the best clinical response;5) Asses safety. Unlike the FDA approved prokinetic agent, metoclopramide, which is also a dopamine antagonist, with antiemetic and prokinetic properties, domperidone has an exellent safety profile for long- term administration. Due to the very restricted accessibility of domperidone in US (through the FDA protocol) many questions related to its efficacy, therapeutic dosing and side effects still remain unanswered. Therefore, we have proposed this study to resolve these questions. PUBLIC HEALTH RELEVANCE: This research underscores the public health significance of gastroparesis (GP) including;the need to develop effective methods for management of GP, the need to identify patients who are at risk of progression to more severe GP, to identify the key cellular changes that lead to GP, and to initiate several novel, therapeutic trials that have the potential to directly influence the quality of life of patients with GP and also in turn provide new knowledge for physicians to treat these patients.